Granulation Flashcards
What is granulation
a size enlargement process by
which the fine powder particles are held together
to form large particles known as granules.
From 0.2-4 mm
Used in tablets and capsules or alone
Why would we use granulation
- Improve flow properties of the mix by size
enlargement - Improve compression properties of the mix
- Prevent segregation of components in the
powder mix - Reduce the production of toxic dust during
powder handling.
5 .Reduce the possibility of ‘cake’ formation
- Increase convenience of transport and
storage:
How does granulation improve the flow properties
By making the surface area smaller
Before granulation, fine powder has high surface
area for contacts among the particles leading to
high cohesive forces. Thus, this powder does not flow
well.
Poor flow will often result in a wide weight variation
within the final product due to variable fill of tablet
dies, etc.
In such cases granulation would provide larger
particles and narrower size distribution
How would granulation improve the compression properties
By the better distribution of binders
Some powders are difficult to compress even if a
readily compressed adhesive binder is included
(as dry powder in the solid-solid mix) in the mix.
Conversely, granules of the same formulation
are often more easily compressed and produce
stronger tablets.
This is attributed to the more efficient distribution
of the adhesive binder (i.e. in solution) within the
granule.
How can we decrease the segregation using granulation
Segregation is primarily due to differences in
size or density of the components, the small
particles concentrating at the base of a
container with the large particles above
them.
An ideal granulation will contain all the
constituents of the mixture in each granule
and separation of the ingredients will not
occur.
However, it is also important to control the
particle size distribution of the granules.
This is because, although the individual
components (i.e. drug and excipients) may not
segregate, if there is a wide size distribution,
granules themselves may segregate,
according to their sizes. → This might result in
large weight variation of final dosage forms.
In other words, granules of different sizes, occupying the
same volume (e.g. in tablet dies, or capsule shells),will
result in different weight of the dosage forms, owing to
their different bulk densities.
How can we reduce caking with granulation
Materials which are slightly hygroscopic may
adhere and form cake if stored as a powder.
Granulation may reduce this hazard as the
granules will be able to absorb some moisture
and yet retain flowability because of their size.
Why is it easier to transfer granules
Granules are denser than the parent powder
mix, (occupy less volume per weight), and thus
more convenient for storage or shipment.
What are the granulation methods
Wet granulation methods which utilize a
liquid in the process
Dry granulation method in which no liquid
is used.
What excipients do we use for granulation
– Diluents, to produce a unit dose weight of
suitable size
– Disintegrating agents which are added to
disintegrate the granule in a liquid medium, e.g.
on ingestion by the patient. – Adhesives (Binders) in the form of a dry powder
may also be added, particularly if dry
granulation is employed.
These ingredients will be mixed before
granulation.
What is wet granulation
Wet granulation involves the massing of the powder
mix using a solvent or a granulating liquid.
The solvents used must be volatile, so that they
can be removed by drying, and non-toxic.
Typical solvents include water, ethanol and
isopropanol either alone or in combination.
The solvent may be used alone or it may contain
a dissolved adhesive (also referred to as binder or
binding agent – e.g. hydroxypropyl
methylcellulose and polyvinylpyrrolidone) which is
used to cause particle adhesion.
Why do we use water as the solvent choice for wet granulation
The primary advantage of water is that it is
nonflammable which means that expensive
safety precautions such as the use of
flame-proof equipment need not to be taken.
What are the disadvantages for using water
The disadvantages of water as a solvent:
1. It may adversely affect drug stability, causing
hydrolysis of susceptible products
2. It needs a longer drying time than organic
solvents. This long drying time increases the
length of the process and may affect stability
because of the extended exposure to heat.
Organic solvents are used when water-sensitive
drugs are processed (as an alternative to dry
granulation), or when a rapid drying time is required.
How do powder particles adhere together
- Adhesion and cohesion forces in immobile liquid films
- Interfacial forces in mobile liquid films
- Solid bridges
- Attractive forces between solid particles
Do the damp powders used on the adhesion and cohesion method help in forming strong bonds?
it is unlikely that
they contribute significantly to the final
granule strength.
What are the interfacial forces stages in granulation process
Three states of water distribution between
particles are observed in granulation process:
a) Pendular
b) Funicular
c) Capillary
a) At low moisture levels, the particles are held
together by lens shaped rings of liquid. These
cause adhesion.
This stage is termed the pendular stage.
b) The funicular state represents an
intermediate stage between the
pendular and capillary states.
c) When all the air has been
displaced from between the
particles the capillary stage is
reached
Note
The state of the powder bed (pendular, funicular,
capillary state) is dependent upon the total
moisture content of the wetted powders.
However, the capillary state may also be reached
by decreasing the separation of the particles.
What is the droplet state
In addition to these states, one more state can be
formed by further addition of liquid, which is the
droplet state to give a suspension. This last state is
not recommended.
How can we form solid bridges
These can be formed by:
a) partial melting
b) hardening binders
c) crystallization of dissolved substances.
How can we use partial melting in the formation in solid bridges
Not considered to be a predominant
mechanism in pharmaceutical materials and it
does not occur in wet granulation
The pressures used in dry granulation methods
may cause melting of low melting point
materials where the particles touch and high
pressures are developed.
When the pressure is relieved, crystallization will
take place and bind the particles together.
How does the hardening binders help in solid bridges
The common mechanism in pharmaceutical wet
granulations.
An adhesive is included in the granulating
solvent. The liquid will form liquid bridges and the
adhesive will harden or crystallize on drying to
form solid bridges to bind the particles.
Adhesives such as polyvinylpyrrolidone, the
cellulose derivatives (such as carboxymethyl
cellulose) function in this way.
How does crystallization help in making solid bridges
The liquid used to mass the powder during wet
granulation may dissolve one of the powdered
ingredients.
When the granules are dried, crystallization of
this material will take place and the dissolved
substance then acts as a hardening binder.
Any material soluble in the granulating liquid
will function in this manner.
What attractive forces happened between solid particles
Electrostatic forces: of importance in causing
powder cohesion and the initial formation of
agglomerates, e.g. during mixing. In general
they do not contribute significantly to the final
strength of the granule.
Van der Waals forces: about four orders of
magnitude greater than electrostatic forces and
contribute significantly to the strength of
granules produced by dry granulation.
Granule growth in the wet granulation procedures may
be described using three general granulation
mechanisms, name them.
Nucleation
Transition
Ball Growth